Carbonyl cyanide 3-chlorophenylhydrazone (CCCP)-induced mitochondrial fission inhibits STING-mediated DNA sensing pathway

Identification: Kwon, Dohyeong


Description

Carbonyl cyanide 3-chlorophenylhydrazone (CCCP)-induced mitochondrial fission inhibits STING-mediated DNA sensing pathway
 
Dohyeong Kwon1, Eunbyeol Park1, Hiromi Sesaki2 and Suk-Jo Kang1,*
1Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 34141, Korea; 2Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore 21205, USA
*Corresponding Author
      
Besides its pivotal role in variety of cellular metabolic functions, the regulatory function of mitochondria in immune response is emerging. Previous study reported that carbonyl cyanide 3-chlorophenylhydrazone (CCCP), the mitochondrial protonophore, suppressed STING-mediated IFN-β production via disrupting mitochondrial membrane potential (MMP). However, how MMP dissipation causes the suppression of the STING pathway remains unknown. Here, we show that CCCP inhibits activation of STING and its downstream signaling molecules, TBK1 and IRF3, but not STING translocation to the perinuclear region. We found that CCCP impairs the interaction between STING and TBK1 and concomitantly triggers mitochondria fission. Importantly, the knockout of the crucial mitochondria fission regulator Drp1 restored the STING activity, indicating that CCCP down-modulates the STING pathway through DRP1-mediated mitochondria fragmentation. Our findings highlight the coupling of the STING signaling platform to mitochondria dynamics
 
 

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